背景:3,4,5-三-O-咖啡酰基奎尼酸(3,4,5-TCQA),一种天然的多酚酸,已被证明对甲型流感病毒(IAV)感染有效。虽然它被发现抑制IAV的神经氨酸酶,它也可能扰乱其他细胞功能,作为多酚酸已经显示出抗氧化剂,抗炎和其他活性。
目的:本研究旨在研究3,4,5-TCQA在细胞水平上的作用。这对于保护宿主细胞免受IAV感染至关重要。
方法:我们研究了3,4,5-TCQA对感染或未感染Pr8IAV的H292细胞的影响。通过RNA测序鉴定主要基因和相关通路。通过qRT-PCR和蛋白质印迹分析证实该途径。使用一氧化氮测量测定法评价抗炎活性。
结果:我们发现3,4,5-TCQA下调H292细胞的免疫反应,并减少了Pr8感染细胞中细胞因子的产生,通过Toll样受体(TLR)信号通路。此外,3,4,5-TCQA在LPS激活的RAW264.7细胞中显示抗炎活性。
结论:总的来说,我们的结果表明,3,4,5-TCQA通过TLR3/7信号通路抑制IAV感染引起的炎症.这为3,4,5-TCQA的抗病毒机制提供了新的见解。
BACKGROUND: 3,4,5-tri-O-caffeoylquinic acid (3,4,5-TCQA), a natural polyphenolic acid, has been shown to be effective against influenza A virus (IAV) infection. Although it was found to inhibit the neuraminidase of IAV, it may also perturb other cellular functions, as polyphenolic acids have shown antioxidant, anti-inflammatory and other activities.
OBJECTIVE: This study aimed to investigate the effect of 3,4,5-TCQA at a cell level, which is critical for protecting host cell from IAV infection.
METHODS: We explored the effect of 3,4,5-TCQA on H292 cells infected or un-infected with Pr8 IAV. The major genes and related pathway were identified through RNA sequencing. The pathway was confirmed by qRT-PCR and western blot analysis. The anti-inflammatory activity was evaluated using nitric oxide measurement assay.
RESULTS: We showed that 3,4,5-TCQA downregulated the immune response in H292 cells, and reduced the cytokine production in Pr8-infected cells, through Toll-like receptor (TLR) signaling pathway. In addition, 3,4,5-TCQA showed anti-inflammatory activity in LPS-activated RAW264.7 cells.
CONCLUSIONS: Collectively, our results indicated that 3,4,5-TCQA suppressed inflammation caused by IAV infection through TLR3/7 signaling pathway. This provides a new insight into the antiviral mechanism of 3,4,5-TCQA.